Lymphoma, Large-Cell, AnaplasticPhase 1NCT03049449
T Cells Expressing a Fully-Human Anti-CD30 Chimeric Antigen Receptor for Treating CD30-Expressing Lymphomas
A Phase 1 study testing Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cells, Cyclophosphamide and Fludarabine in people with Lymphoma, Large-Cell, Anaplastic and Enteropathy-Associated T-Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Background: Improved treatments for a variety of treatment-resistant, TNFRSF8 (CD30)-expressing malignancies including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing lymphomas are needed. Read more about this study
- Who is it for?
- Ages 18 to 73 years
- Conditions the study is for
- Lymphoma, Large-Cell, Anaplastic, Enteropathy-Associated T-Cell Lymphoma, Lymphoma, Large B-Cell, Diffuse
- What is being tested?
- Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cells, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Mar 2017to 26 Jan 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 73 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Malignancy Criteria:
- Patients must have anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy-associated T-cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma, nasal type
- Clear TNFRSF8 (CD30) expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient's malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-B-lymphocyte antigen CD20 (CD20) monoclonal antibody.
- Patients must have measurable malignancy as defined by at least one of the criteria below.
- Lymphoma mass that is measurable (minimum 1.5 cm in largest diameter) by computed tomography (CT) scan is required unless bone marrow lymphoma is detectable.
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- For a lymphoma mass to count as measurable malignancy, it must have abnormally increased metabolic activity when assessed by positron emission tomography (PET) scan.
- For lymphoma with only bone marrow involvement, no mass is necessary, but if a mass is not present, bone marrow malignancy must be detectable by flow cytometry.
- Other Inclusion Criteria:
- Greater than or equal to 18 years of age and less than or equal to age 73.
- Able to understand and sign the Informed Consent Document.
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-2
- Room air oxygen saturation of 92% or greater
- Male patients and must be willing to practice birth control from the time of enrollment on this study and for four months following the final CAR T-cell infusion. Pre-menopausal patients (female patients who have had a menstrual period within the last year) must be willing to practice birth control from the time of enrollment and for one year following the final CAR T cell infusion.
- Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for Human T-cell lymphotropic virus type 1 (HTLV-1).
- Negative for hepatitis B surface antigen. Positive hepatitis B tests can be further evaluated by confirmatory tests; and if confirmatory tests are negative, the patient can be enrolled.
- Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of ribonucleic acid (RNA) by Reverse transcription polymerase chain reaction (RT-PCR) and be Hepatitis C (HCV) RNA negative to be enrolled.
- A patient with a prior history of hepatitis B or a prior history of hepatitis C may participate, as long as the patient s viral hepatitis has been treated, and the patient has no detectable Hepatitis B (HBV) deoxyribonucleic acid (DNA) or HCV RNA.
- At time of protocol enrollment, the patient should be negative for cytomegalovirus (CMV) by antibody testing or by PCR. In case of disagreement between these 2 CMV tests, the tests will be repeated, and Dept. of Laboratory Medicine consulted.
- Absolute neutrophil count greater than or equal to 1000/mm^3 without the support of filgrastim or other growth factors.
- Platelet count greater than or equal to 55,000/mm^3
- Hemoglobin greater than 8.0 g/dl. Transfusion support is allowed.
- Less than 5% malignant cells in the peripheral blood leukocytes
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated.
- Serum creatinine less than or equal to 1.6 mg/dL.
- Total bilirubin less than or equal to 2.0 mg/dl.
- At least 14 days must have elapsed since any prior systemic therapy prior to apheresis and prior to the initiation of chemotherapy (including systemic corticosteroids at doses greater than prednisone 5 mg/day or the equivalent corticosteroid doses). Because this protocol requires collection of autologous blood cells by leukapheresis in order to prepare CAR T cells, systemic anti-malignancy therapy including systemic corticosteroid therapy at doses greater than prednisone 5 mg/day or the equivalent corticosteroid doses is not allowed within 14 days prior to the required leukapheresis. NOTE: Because of the long half-life and potential to affect CAR T-cells, 30 days must elapse from the time of administration of anti-Programmed cell death protein 1 (PD-1) or anti-Programmed death-ligand 1 (PD-L1) antibodies or other agents that in the opinion of the PI can stimulate immune activity and infusion of CAR T-cells.
- Normal cardiac ejection fraction (greater than or equal to 50% by echocardiography) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks of the start of the treatment protocol.
- Patients must not take corticosteroids at doses higher than 5 mg/day of prednisone or the equivalent for 14 days before apheresis, and for 14 days prior to the conditioning chemotherapy regimen.
- Patients must be willing to undergo endotracheal intubation, mechanical ventilation, dialysis, cardiopulmonary resuscitation (CPR), and electrical defibrillation. Patients must be willing to receive vasopressor drugs and all other standard intensive care unit interventions. Any living will must be amended to allow these interventions, or the patient will not eligible.
- Patients who have been treated on other protocols of genetically-modified T-cells at the National Institutes of Health (NIH) only are potentially eligible under these conditions:
- At least 6 months have elapsed since the last genetically-modified T-cell therapy that the patient received and there is no evidence of replication-competent retroviruses (evidence must be provided from prior NIH gene-therapy protocol Principal Investigator) and persisting genetically-modified T cells are not detectable in the patient's blood (evidence must be provided by prior NIH gene-therapy protocol Principal Investigator).
- Additional Inclusion Criteria Pertinent Only for Patients with Prior Allogeneic Transplantation:
- Recipients must have received an 9/10 or 10/10 HLA-matched sibling allogeneic hematopoietic stem cell transplant, or a 9/10 or 10/10 HLA-matched unrelated donor (URD) allo-HSCT for an eligible CD30+ lymphoma.
- Donor T cell engraftment after allo-Hematopoietic stem-cell transplantation (HSCT)(>90% donor chimerism of the T-cell compartment).
- Patients must be at least 90 days post-transplant.
- Patients must be off all systemic immunosuppressive drugs including corticosteroids at doses of greater than 5 mg/day prednisone or equivalent, if given for treatment of graft versus host disease, for at least 28 days prior to protocol enrollment and must remain off immunosuppressive drugs while enrolled on the protocol. Patients must not be taking any systemic steroids at doses greater than 5 mg/day prednisone or equivalent at all for 14 days prior to apheresis and initiation of chemotherapy. Topical corticosteroid preparations applied to the skin such as solutions, creams, and ointments are allowed. Inhaled corticosteroids are allowed, and corticosteroid eye drops are allowed.
- Prior donor lymphocyte infusions (DLIs) are not necessary.
- Either no evidence of graft versus host (GVHD) or minimal clinical evidence of acute GVHD and chronic GVHD while off of systemic immunosuppressive therapy for at least 28 days. Minimal clinical evidence of acute GVHD defined as grade 0 to I acute GVHD 109 Minimal evidence of chronic GVHD is defined as mild global score chronic GVHD (as defined by the 2005 NIH consensus project) or no chronic GVHD .107 Subjects with disease that is controlled to stage I acute GVHD or to mild global score chronic GVHD with local topical cutaneous steroids will be eligible for enrollment.
Who cannot join
- Patients with Hodgkin lymphoma are no longer eligible for participation (as of amendment G, Protocol version: 08/12/2019).
- Patients that require urgent therapy due to tumor mass effects or spinal cord compression.
- Patients with lymphoma masses 10.0 cm or larger in longest diameter will not be eligible.
- Patients that have active hemolytic anemia.
- Patients who are currently taking any medications for systemic anticoagulation other than aspirin will not be eligible.
- Patients with second malignancies in addition to their lymphoma are not eligible if the second malignancy has required treatment (including maintenance therapy) within the past 4 years or is not in complete remission. There are two exceptions to this criterion:
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- successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant. Women of child-bearing potential are defined as all women except women who are postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as women over the age of 55 who have not had a menstrual period in at least 1 year.
- Active uncontrolled systemic infections (defined as infections causing fevers and infections requiring intravenous antibiotics when the intravenous antibiotics have been administered for less than 72 hours); active coagulation disorders or other major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system; history of myocardial infarction; history of idiopathic ventricular tachycardia or ventricular fibrillation in the past 12 months or history of ventricular tachycardia or ventricular fibrillation (VT/VF) associated with VT/VF risk factors (e.g., QT prolongation and cardiomyopathy); active cardiac arrhythmias (Active atrial fibrillation is not allowed, but resolved atrial fibrillation is allowed.); active obstructive or restrictive pulmonary disease; or active autoimmune diseases such as rheumatoid arthritis.
- Patients will not be seen for screening appointments or enrolled on the protocol if they have been hospitalized within the 7 days prior to the screening appointment or the date of protocol enrollment.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) , unless the immunodeficiency has been cured by allogeneic stem cell transplant.
- Systemic corticosteroid therapy at doses greater than 5 mg/day of prednisone or the equivalent dose is not allowed within 14 days prior to the required leukapheresis, or the initiation of the conditioning chemotherapy regimen. Corticosteroid creams, ointments, and eye drops are allowed.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Patients with current central nervous system (CNS) involvement by malignancy (either by imaging or cerebrospinal fluid involvement or biopsy-proven).
- Patients currently taking anticoagulants.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Anti-CD30 CAR T Cells With Fully-human Binding Domains for Treating CD30-expressing Lymphomas Including Anaplastic Large Cell Lymphomas
Background:
- Improved treatments for a variety of treatment-resistant, TNFRSF8 (CD30)-expressing malignancies including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing lymphomas are needed.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen B-lymphocyte antigen CD19 (CD19) have caused complete remissions in a small number of patients with lymphoma. These results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in humans.
- CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which allows selection of CD30-expressing malignancies for treatment.
- CD30 is not known to be expressed by normal cells except for a small number of activated lymphocytes.
- We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice.
- This particular CAR has not been tested before in humans.
- Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of a small number of normal activated lymphocytes is possible, and unknown toxicities are also possible.
Read more
Objectives:
Primary
-Determine the safety and feasibility of administering T-cells expressing a novel fully human anti-CD30 CAR to patients with advanced CD30-expressing lymphomas.
Eligibility:
- Patients must have anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy associated T-cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma, nasal type
- Patients must have malignancy that is both measurable on a computed tomography (CT) scan with a largest diameter of at least 1.5 cm and possessing increased metabolic activity detectable by positron emission tomography (PET) scan. Alternatively, patients with lymphoma detected by flow cytometry of bone marrow are eligible.
- Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection fraction.
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 is required.
- No active infections are allowed including evidence of active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. At the time of protocol enrollment patients must be seronegative for cytomegalovirus (CMV) by antibody testing or must have a negative blood CMV polymerase chain reaction (PCR).
- Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated.
- At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and initiation of required leukapheresis.
- Clear CD30 expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-CD20 monoclonal antibody.
- Patients who have never had an allogeneic hematopoietic stem cell transplant as well as patients who have had a 9/10 or 10/10 human leukocyte antigen (HLA)-matched sibling or a 9/10 or 10/10 HLA- matched unrelated donor hematopoietic stem cell transplant are potentially eligible.
- Women who are pregnant or plan to become pregnant will be excluded.
Read the detailed description
Background:
- Improved treatments for a variety of treatment-resistant, TNFRSF8 (CD30)-expressing malignancies including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing lymphomas are needed.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen B-lymphocyte antigen CD19 (CD19) have caused complete remissions in a small number of patients with lymphoma. These results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in humans.
- CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which allows selection of CD30-expressing malignancies for treatment.
- CD30 is not known to be expressed by normal cells except for a small number of activated lymphocytes.
- We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice.
- This particular CAR has not been tested before in humans.
- Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of a small number of normal activated lymphocytes is possible, and unknown toxicities are also possible.
Objectives:
Primary
-Determine the safety and feasibility of administering T-cells expressing a novel fully-human anti-CD30 CAR to patients with advanced CD30-expressing lymphomas.
Eligibility:
- Patients must have anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy-associated T-cell lymphoma, or extranodal natural killer (NK)//T-cell lymphoma, nasal type
- Patients must have malignancy that is both measurable on a computed tomography (CT) scan with a largest diameter of at least 1.5 cm and possessing increased metabolic activity detectable by positron emission tomography (PET) scan. Alternatively, patients with lymphoma detected by flow cytometry of bone marrow are eligible.
- Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection fraction.
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 is required.
- No active infections are allowed including evidence of active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. At the time of protocol enrollment, patients must be seronegative for cytomegalovirus (CMV) by antibody testing or must have a negative blood CMV polymerase chain reaction (PCR).
- Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated.
- At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and initiation of required leukapheresis.
- Clear CD30 expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-CD20 monoclonal antibody.
- Patients who have never had an allogeneic hematopoietic stem cell transplant as well as patients who have had a 9/10 or 10/10 human leukocyte antigen (HLA)-matched sibling or a 9/10 or 10/10 HLA- matched unrelated donor hematopoietic stem cell transplant are potentially eligible.
- Women who are pregnant or plan to become pregnant will be excluded.
Design:
- This is a phase I dose-escalation trial.
- Patients will undergo leukapheresis.
- T cells obtained by leukapheresis will be genetically modified to express an anti-CD30 CAR.
- Patients will receive a lymphocyte-depleting chemotherapy conditioning regimen with the intent of enhancing the activity of the infused anti-CD30 CAR-expressing T cells.
- A chemotherapy conditioning regimen of cyclophosphamide and fludarabine will be administered prior to all CAR T-Cell infusions. Fludarabine will be given on the same days as the cyclophosphamide.
- Two days after the chemotherapy ends, patients will receive an infusion of anti-CD30-CAR-expressing T cells.
- The initial dose level of this dose-escalation trial will be 0.3x10(6) CAR+ T cells/kg of recipient bodyweight for Cohort 1. The initial dose level will be 1 x 10 (6) CAR+T cells/kg for Cohort 2.
- The cell dose administered will be escalated until a maximum tolerated dose is determined.
- Following the T-cell infusion, there is a mandatory 9-day inpatient hospitalization to monitor for toxicity.
- Outpatient follow-up is planned for 2 weeks and 1, 2, 3, 4, 6, 9, and 12 months after the CAR T-cell infusion. Long-term gene-therapy follow-up consisting of yearly visits to a doctor near the patients home for 4 more years and then yearly telephone contact for 10 additional years will be required.
- As of Amendment E (Protocol version: 08/03/2018), repeat treatments consisting of the conditioning chemotherapy followed by a CAR T-cell infusion at the maximum tolerated dose (MTD) for the patients cohort are allowed for eligible patients with any best responses except continuing complete remission or progressive malignancy.
- Re-enrollment will be allowed for a small number of subjects.
- Conditions
- Lymphoma, Large-Cell, Anaplastic, Enteropathy-Associated T-Cell Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Extranodal NK-T-Cell, Lymphoma, T-Cell, Peripheral
- Being tested
- Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cells, Cyclophosphamide, Fludarabine
- Keywords
- Gray Zone Lymphoma, Immunotherapy, Peripheral T-Cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell lymphoma
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic, Enteropathy-Associated T-Cell Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Extranodal NK-T-Cell, Lymphoma, T-Cell, Peripheral, Immunoblastic Lymphadenopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cellsBiological
Dose-escalation trial starting dose: 0.3x10^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) (up to a maximum dose of 18x10^6 CAR+ T cells/kg) infuse on day 0
CyclophosphamideDrug
Also called Cytoxan
300 or 500 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3
FludarabineDrug
Also called Fludara
30 mg/m^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3
| Study group | Role | What they receive |
|---|---|---|
| Chimeric Antigen Receptor (CAR)+ T cells | Experimental | All patients will be receiving starting dose: 0.3x10^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) (up to a maximum dose of 18x10^6 CAR+ T cells/kg) infuse on day 0 and Cyclophosphamide: 300 or 500 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3 Receives: Biological: Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cells; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose of Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) in Participants With Advanced CD30-expressing Lymphomas
Maximum tolerated dose is defined as the dose at which a maximum of 1 of 6 participants has a dose-limiting toxicity (DLT). A DLT is defined as toxicities occurring within 30 days of CAR T-cell infusion. DLT's are Grade 3 or Grade 4 toxicities possibly, probably, or definitely related to either the anti-CD30 CAR T cells or the fludarabine and cyclophosphamide chemotherapy conditioning regimen and lasting more than 7 days. A DLT will only be considered in participants who have received CAR T-cell infusions.
Measured: 4-5 weeks after first dose
Secondary outcomes (2)
Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells
Peak percentage and the percentage 1 month after infusion of peripheral blood mononuclear cells (PBMC) that expressed the Chimeric Antigen Receptor (CAR) T-cells assessed by polymerase chain reaction (PCR).
Measured: From time of infusion until 1 month after infusion
Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response
Response was measured using the Cheson et al. Revised Response Criteria for Malignant Lymphoma, Journal of Clinical Oncology 2007 and Recommendations for Initial Evaluation, Staging, and Response Assessment of Non-Hodgkin Lymphoma: The Lugano Classification Journal of Clinical Oncology, 2014). Complete Response (CR) is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial Response (PR) is ≥ 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. Progressive Disease (PD) ≥ 50% increase from nadir in the sum of the products of at least two lymph nodes, or appearance of a new lesion greater than 1.5 cm in any axis even if other lesions are decreasing in size. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: Responses will be assessed as long as the patient is on-study at the following time-points: 1, 2, 3, 4, 6, 9, and 12 months after CAR T-cell infusion. Then responses were assessed every 6 months up until 3 years after CAR T-cell infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
17 Mar 201726 Jan 2022
- First posted10 Feb 2017
- Study start17 Mar 2017
- Primary completion26 Jan 2022
- Study completion26 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lymphoma, Large-Cell, AnaplasticStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, James Kochenderfer, M.D., National Cancer Institute (NCI)
- Investigators
- James N Kochenderfer, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03049449
- Sponsor's protocol ID
- 170048
- Other IDs
- 17-C-0048
- Status last verified
- Dec 2022
- First submitted
- 9 Feb 2017
- Last updated
- 18 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share coded, linked data in an National Institutes of Health (NIH)-funded or approved public repository. Coded, linked data in Biomedical Translational Research Information System (BTRIS).
Publications
Brudno JN, Natrakul DA, Karrs J, Patel N, Maass-Moreno R, Ahlman MA, Mikkilineni L, Mann J, Stroncek DF, Highfill SL, Fromm GC, Patel R, Pittaluga S, Kochenderfer JN. Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas: results of a phase 1 trial. Blood Adv. 2024 Feb 13;8(3):802-814. doi: 10.1182/bloodadvances.2023011470.
PubMed 37939262
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-CD30 CAR T Cells With Fully-human Binding Domains for Treating CD30-expressing Lymphomas Including Anaplastic Large Cell Lymphomas
- ClinicalTrials.gov ID
- NCT03049449
- Acronym / sponsor ID
- 170048
- Conditions
- Lymphoma, Large-Cell, Anaplastic, Enteropathy-Associated T-Cell Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Extranodal NK-T-Cell, Lymphoma, T-Cell, Peripheral
- Keywords
- Gray Zone Lymphoma, Immunotherapy, Peripheral T-Cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 17 Mar 2017 (actual)
- Primary completion
- 26 Jan 2022 (actual)
- Study completion
- 26 Jan 2022 (actual)
- First posted
- 10 Feb 2017 (actual)
- Results
- Posted 25 May 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Improved treatments for a variety of treatment-resistant, TNFRSF8 (CD30)-expressing malignancies including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing lymphomas are needed.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen B-lymphocyte antigen CD19 (CD19) have caused complete remissions in a small number of patients with lymphoma. These results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in humans.
- CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which allows selection of CD30-expressing malignancies for treatment.
- CD30 is not known to be expressed by normal cells except for a small number of activated lymphocytes.
- We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice.
- This particular CAR has not been tested before in humans.
- Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of a small number of normal activated lymphocytes is possible, and unknown toxicities are also possible.
Objectives:
Primary
-Determine the safety and feasibility of administering T-cells expressing a novel fully human anti-CD30 CAR to patients with advanced CD30-expressing lymphomas.
Eligibility:
- Patients must have anaplastic large cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy associated T-cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma, nasal type
- Patients must have malignancy that is both measurable on a computed tomography (CT) scan with a largest diameter of at least 1.5 cm and possessing increased metabolic activity detectable by positron emission tomography (PET) scan. Alternatively, patients with lymphoma detected by flow cytometry of bone marrow are eligible.
- Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection fraction.
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 is required.
- No active infections are allowed including evidence of active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. At the time of protocol enrollment patients must be seronegative for cytomegalovirus (CMV) by antibody testing or must have a negative blood CMV polymerase chain reaction (PCR).
- Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated.
- At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and initiation of required leukapheresis.
- Clear CD30 expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-CD20 monoclonal antibody.
- Patients who have never had an allogeneic hematopoietic stem cell transplant as well as patients who have had a 9/10 or 10/10 human leukocyte antigen (HLA)-matched sibling or a 9/10 or 10/10 HLA- matched unrelated donor hematopoietic stem cell transplant are potentially eligible.
- Women who are pregnant or plan to become pregnant will be excluded.
Detailed description
Background:
- Improved treatments for a variety of treatment-resistant, TNFRSF8 (CD30)-expressing malignancies including Hodgkin lymphoma, anaplastic large cell lymphoma, and other CD30- expressing lymphomas are needed.
- T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens.
- Autologous T cells genetically modified to express CARs targeting the B-cell antigen B-lymphocyte antigen CD19 (CD19) have caused complete remissions in a small number of patients with lymphoma. These results demonstrate that CAR-expressing T cells can have anti-lymphoma activity in humans.
- CD30 expression can be easily detected by immunohistochemistry on lymphoma cells, which allows selection of CD30-expressing malignancies for treatment.
- CD30 is not known to be expressed by normal cells except for a small number of activated lymphocytes.
- We have constructed a novel fully-human anti-CD30 CAR that can specifically recognize CD30-expressing target cells in vitro and eradicate CD30-expressing tumors in mice.
- This particular CAR has not been tested before in humans.
- Possible toxicities include cytokine-associated toxicities such as fever, hypotension, and neurological toxicities. Elimination of a small number of normal activated lymphocytes is possible, and unknown toxicities are also possible.
Objectives:
Primary
-Determine the safety and feasibility of administering T-cells expressing a novel fully-human anti-CD30 CAR to patients with advanced CD30-expressing lymphomas.
Eligibility:
- Patients must have anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy-associated T-cell lymphoma, or extranodal natural killer (NK)//T-cell lymphoma, nasal type
- Patients must have malignancy that is both measurable on a computed tomography (CT) scan with a largest diameter of at least 1.5 cm and possessing increased metabolic activity detectable by positron emission tomography (PET) scan. Alternatively, patients with lymphoma detected by flow cytometry of bone marrow are eligible.
- Patients must have a creatinine of 1.6 mg/dL or less and a normal cardiac ejection fraction.
- An Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 is required.
- No active infections are allowed including evidence of active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. At the time of protocol enrollment, patients must be seronegative for cytomegalovirus (CMV) by antibody testing or must have a negative blood CMV polymerase chain reaction (PCR).
- Absolute neutrophil count greater than or equal to 1000/micro L, platelet count greater than or equal to 55,000/micro L, hemoglobin greater than or equal to 8g/dL
- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated.
- At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids above 5 mg/day of prednisone or equivalent corticosteroid dose) and initiation of required leukapheresis.
- Clear CD30 expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient s malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-CD20 monoclonal antibody.
- Patients who have never had an allogeneic hematopoietic stem cell transplant as well as patients who have had a 9/10 or 10/10 human leukocyte antigen (HLA)-matched sibling or a 9/10 or 10/10 HLA- matched unrelated donor hematopoietic stem cell transplant are potentially eligible.
- Women who are pregnant or plan to become pregnant will be excluded.
Design:
- This is a phase I dose-escalation trial.
- Patients will undergo leukapheresis.
- T cells obtained by leukapheresis will be genetically modified to express an anti-CD30 CAR.
- Patients will receive a lymphocyte-depleting chemotherapy conditioning regimen with the intent of enhancing the activity of the infused anti-CD30 CAR-expressing T cells.
- A chemotherapy conditioning regimen of cyclophosphamide and fludarabine will be administered prior to all CAR T-Cell infusions. Fludarabine will be given on the same days as the cyclophosphamide.
- Two days after the chemotherapy ends, patients will receive an infusion of anti-CD30-CAR-expressing T cells.
- The initial dose level of this dose-escalation trial will be 0.3x10(6) CAR+ T cells/kg of recipient bodyweight for Cohort 1. The initial dose level will be 1 x 10 (6) CAR+T cells/kg for Cohort 2.
- The cell dose administered will be escalated until a maximum tolerated dose is determined.
- Following the T-cell infusion, there is a mandatory 9-day inpatient hospitalization to monitor for toxicity.
- Outpatient follow-up is planned for 2 weeks and 1, 2, 3, 4, 6, 9, and 12 months after the CAR T-cell infusion. Long-term gene-therapy follow-up consisting of yearly visits to a doctor near the patients home for 4 more years and then yearly telephone contact for 10 additional years will be required.
- As of Amendment E (Protocol version: 08/03/2018), repeat treatments consisting of the conditioning chemotherapy followed by a CAR T-cell infusion at the maximum tolerated dose (MTD) for the patients cohort are allowed for eligible patients with any best responses except continuing complete remission or progressive malignancy.
- Re-enrollment will be allowed for a small number of subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chimeric Antigen Receptor (CAR)+ T cells | Experimental | Biological: Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cells, Drug: Cyclophosphamide, Drug: FludarabineAll patients will be receiving starting dose: 0.3x10^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) (up to a maximum dose of 18x10^6 CAR+ T cells/kg) infuse on day 0 and Cyclophosphamide: 300 or 500 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 and Fludarabine: 30 mg/m^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3 |
Who may qualify
- Ages
- 18 to 73 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Patients must have anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma not otherwise specified, diffuse large B-cell lymphoma not otherwise specified, primary mediastinal B-cell lymphoma, grey zone lymphoma, enteropathy-associated T-cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma, nasal type
- Clear TNFRSF8 (CD30) expression must be detected on 75% or more of malignant cells from either bone marrow or lymphoma mass by flow cytometry or immunohistochemistry. The patient's malignancy will need to be assessed for CD30 expression by flow cytometry or immunohistochemistry performed at the National Institutes of Health (NIH). If unstained, paraffin-embedded bone marrow or lymphoma sections are available from prior biopsies, these can be used to determine CD30 expression by immunohistochemistry; otherwise, patients will need to come to the NIH for a biopsy to determine CD30 expression. The sample for CD30 expression can come from a biopsy obtained at any time before enrollment, unless the patient has received a prior anti-CD30 monoclonal antibody, in which case the sample must come from a biopsy following completion of the most recent anti-CD30 monoclonal antibody treatment.
- Eligible patients with diffuse large B-cell lymphoma or primary mediastinal B-cell lymphoma must have received 2 prior treatment regimens at least 1 of which included an anthracycline and an anti-B-lymphocyte antigen CD20 (CD20) monoclonal antibody.
- Patients must have measurable malignancy as defined by at least one of the criteria below.
- Lymphoma mass that is measurable (minimum 1.5 cm in largest diameter) by computed tomography (CT) scan is required unless bone marrow lymphoma is detectable.
Key exclusion criteria (15 listed)
- Patients with Hodgkin lymphoma are no longer eligible for participation (as of amendment G, Protocol version: 08/12/2019).
- Patients that require urgent therapy due to tumor mass effects or spinal cord compression.
- Patients with lymphoma masses 10.0 cm or larger in longest diameter will not be eligible.
- Patients that have active hemolytic anemia.
- Patients who are currently taking any medications for systemic anticoagulation other than aspirin will not be eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cellsDose-escalation trial starting dose: 0.3x10^6 Chimeric Antigen Receptor (CAR)+ T cells/kg (weight based dosing) (up to a maximum dose of 18x10^6 CAR+ T cells/kg) infuse on day 0 | Biological | Chimeric Antigen Receptor (CAR)+ T cells |
| CyclophosphamideAlso: Cytoxan300 or 500 mg/m^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3 | Drug | Chimeric Antigen Receptor (CAR)+ T cells |
| FludarabineAlso: Fludara30 mg/m^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4, and -3 | Drug | Chimeric Antigen Receptor (CAR)+ T cells |
Primary outcome
Maximum Tolerated Dose of Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) in Participants With Advanced CD30-expressing Lymphomas
Time frame: 4-5 weeks after first dose
Maximum tolerated dose is defined as the dose at which a maximum of 1 of 6 participants has a dose-limiting toxicity (DLT). A DLT is defined as toxicities occurring within 30 days of CAR T-cell infusion. DLT's are Grade 3 or Grade 4 toxicities possibly, probably, or definitely related to either the anti-CD30 CAR T cells or the fludarabine and cyclophosphamide chemotherapy conditioning regimen and lasting more than 7 days. A DLT will only be considered in participants who have received CAR T-cell infusions.
2 secondary outcomes
Peak Percentage and Persistence at 1 Month of Peripheral Blood Mononuclear Cells (PBMC) That Expressed the Chimeric Antigen Receptor (CAR) T-cells
Time frame: From time of infusion until 1 month after infusion
Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progression as Their Best Response
Time frame: Responses will be assessed as long as the patient is on-study at the following time-points: 1, 2, 3, 4, 6, 9, and 12 months after CAR T-cell infusion. Then responses were assessed every 6 months up until 3 years after CAR T-cell infusion.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37939262Brudno JN, Natrakul DA, Karrs J, Patel N, Maass-Moreno R, Ahlman MA, Mikkilineni L, Mann J, Stroncek DF, Highfill SL, Fromm GC, Patel R, Pittaluga S, Kochenderfer JN. Transient responses and significant toxicities of anti-CD30 CAR T cells for CD30+ lymphomas: results of a phase 1 trial. Blood Adv. 2024 Feb 13;8(3):802-814. doi: 10.1182/bloodadvances.2023011470.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. We will share coded, linked data in an National Institutes of Health (NIH)-funded or approved public repository. Coded, linked data in Biomedical Translational Research Information System (BTRIS).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James N Kochenderfer, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) T cells, Cyclophosphamide and Fludarabine in people with Lymphoma, Large-Cell, Anaplastic and Enteropathy-Associated T-Cell Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 40 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose of Anti-Tumor Necrosis Factor (TNF) Receptor Superfamily Member 8 (CD30) Chimeric Antigen Receptor (CAR) in Participants With Advanced CD30-expressing Lymphomas (time frame: 4-5 weeks after first dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03049449, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2023.